Agents potentially affecting cell surface structures are designed, synthesized, and examined for anti-cancer activity in mouse tumor model systems including L1210 leukemia, Friend erythroleukemia, and Ehrlich carcinoma in vivo and in vitro. Active agents are subjected to detailed biochemical and immunological studies to ascertain mechanisms by which anti-cancer effects are obtained. Active agents at this point include esters of 1-chloro- and 1-bromo-3-hydroxyacetone (benzoate, p-nitrobenzoate, and 3,5-dinitro-benzoate), and N-halo-acetyl-analogs of N-acetyl-hexosamines (bromo- and chloro-analogs of N-acetyl-glucosamine and N-acetyl-galactoamine as the lipophilic tetra-O-acetates. These agents cure Ehrlich carcinoma in vivo by single injection if host animals are immune-competent. Such animals exhibit strong resistance to rechallenge. Friend erythroleukemia cells treated in culture with 1-chloro-3-hydroxyacetone benzoate (C1HAB) and implanted into syngeneic host mice, confer protective immunity to rechallenge with Friend leukemia cells. Under similar conditions in vitro, altered L1210 leukemia cells suppress resistance to rechallenge in semi-syngeneic hosts, and generate no apparent in vivo effects in syngeneic hosts. It is postulated that these agents exert their effects as lipophilic alkylating agents reactive with cell surface thiol groups. C1HAB radioactively labelled reacts very rapidly with free thiol groups and much more slowly with amino groups at pH 7, and is incorporated into L1210 cells maximally within 20 minutes in such a manner that 30% of the label can be released by mild trypsin treatment. Such treated cells do not generate an allogeneic anti-H2 response when implanted into C57 mice, but continue to generate a syngeneic anti-tumor antigen response in syngeneic hosts. There is no apparent direct effect on lipid end-product metabolites in cell homogenates, suggesting the primary site of modification may be at protein thiol groups.